US8639306B2 - Noninvasive eye-property monitoring, including aqueous-humor glucose monitoring as an indication of blood glucose level - Google Patents
Noninvasive eye-property monitoring, including aqueous-humor glucose monitoring as an indication of blood glucose level Download PDFInfo
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- US8639306B2 US8639306B2 US13/366,299 US201213366299A US8639306B2 US 8639306 B2 US8639306 B2 US 8639306B2 US 201213366299 A US201213366299 A US 201213366299A US 8639306 B2 US8639306 B2 US 8639306B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
- A61B5/14507—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
- A61B5/6813—Specially adapted to be attached to a specific body part
- A61B5/6814—Head
- A61B5/6821—Eye
Definitions
- the present invention pertains to noninvasive eye-property monitoring, and more particularly to the noninvasive monitoring of various eye properties through noting how, in an observed light reflection from the eye, certain characteristics of selected and controlled light which has been directed toward the eye have become affected in the process of the directed light's engagement with the eye. While there are many useful applications for the practice of this invention, I have found that its methodology offers particular, and notably high, utility in relation to the monitoring of aqueous-humor glucose content as an indication of blood glucose level— an important, medically-associated diagnostic task.
- aqueous humor aqueous humor
- eye “properties” associated with the aqueous humor include uric acid, ascorbate, lactic acid, inorganic phosphates, bicarbonates, chlorides, and urea.
- glucose concentration is usually measured by extracting a drop of blood and subjecting it to a form of chemical analysis.
- the index of refraction of the aqueous changes proportionately. Further, the amount of change in the index is different for different wavelengths of light.
- the proportion of incident light that is reflected depends upon the ratio of the indices of refraction of the two substances. Therefore, if the glucose concentration in the aqueous changes, the intensity of light reflected from the interface between the back surface of the cornea and the aqueous will change, and the change will be different for different wavelengths.
- the system and methodology of the present invention in the illustrative glucose-detection/monitoring setting described below, produce information contained in light-associated, optical-activity-affected, reflected light which furnishes a measure of aqueous glucose concentration—which information may be based upon either changes in index of refraction or of absorption or both. With appropriate calibration, it makes no difference which, or whether both, of these two optical phenomena contribute to this information. Such calibration may be performed by conducting a conventional blood glucose concentration test, and then, essentially at the same time, implementing eye-reflection-condition monitoring in accordance with the invention to compare data.
- an eye-property monitoring system and methodology collectively featuring the enabling and practicing of the steps including (1) illuminating the eye from at least one light source whose wavelength interacts with internal eye properties in an optically active manner, (2) controlling, to make substantially known and stable, at a predetermined setting, the operating power/light-output level of the source, (3) by such illuminating, producing light-source eye reflections including (a) multiple internal reflections within the outer structure of the eye, and (b) at least one resulting outbound reflection, (4) monitoring the outbound-reflection to detect therein the reflection level associated with the at least one source, and (5) associating such detected reflection level as an indication of certain eye properties.
- an eye-property monitoring method including (a) in a seriatim manner, illuminating the eye (one or more region(s) on the limbus) from two or more, different-wavelength light sources whose respective wavelengths interact with internal eye properties in optically differentiated manners, (b) adjusting the operating levels of the sources to a predetermined relative setting, (c) by such illuminating, producing seriatim-light-source eye reflections including multiple internal reflections within the outer structure of the eye, and at least one resulting outbound reflection, (d) monitoring the outbound-reflection to detect therein the relative reflection levels associated with the sources, and (e) associating such detected, relative reflection levels as an indication of certain eye properties.
- a blood glucose monitoring method including (a) in an alternating manner, illuminating the eye (again, one or more region(s) on the limbus) from two, different-wavelength light sources, one of which has a wavelength to which glucose is more optically active than it is to the wavelength of the other source, (b) adjusting the operating levels of the two sources to a predetermined relative setting, (c) by such illuminating, producing eye reflections including multiple internal reflections within the outer structure of the eye, and at least one resulting outbound reflection, and (d) monitoring a selected condition of the outbound reflection as an indication of blood glucose level.
- the system-implementable methodology of the invention is preferably computer-based, and includes both (1) computer controlling of the illuminating, controlling and adjusting steps, and (2) computer conducting of the monitoring step.
- Illuminating is performed by directing light from the employed light sources along a common (in the case of two or more sources) illumination path which lies at an angle relative to the eye's line of sight, and the producing step is accomplished to effect eye reflections occurring within the cornea of the eye, and even more particularly is conducted so as to effect eye reflections, including multiple reflections, from the optical interface existing between the cornea (its inside, or back surface, or side) and the aqueous humor of the eye.
- the thickness, or the index of refraction, or both, of the endothelial cells changes with glucose concentration, that will also affect monitoring measurement, and may do so perhaps beneficially, and maybe even strongly.
- Appropriate implementation-system calibration will take into account this potentially very useful phenomenon.
- optical-reflection physics may actually be quite more complex than simple, in the sense that “internal-eye-structure” reflections produced by practice of the invention might include both (a) reflections from the optical interface existing between the cornea and the endothelial cells, and (b) reflections between the endothelial cells and the aqueous. It is also possible, in relation to monitoring glucose, that glucose concentration might affect the properties of the endothelial cells, for example in a manner, such as by cell-layer thickening, affecting reflection intensity. All of these considerations, however, complexities set aside from detailed analysis, will not affect the viability of invention practice with the earlier mentioned system calibration steps taken with respect to each examined person.
- optical, and associated computer-control, system which implements the methodology of the invention may be relatively simple in construction, and can readily lend itself to economical and compact construction—features which those skilled in the art will easily understand. Additionally, those skilled in the art will immediately recognize the possibilities for numerous variations in systemic and detailed methodologic practices that will lie well within the scope of the invention's basic contributions to the art, as expressed very generally above, and these matters testify to the important flexibility and versatility of the invention.
- the flow paths, or lines, along which incident illumination coming respectively from these sources need not exactly match one another, and while incident illumination should always strike a region on the limbus of eye, the incident beams need not necessarily strike exactly the same region of the limbus.
- FIG. 1 is a simplified, block/schematic diagram illustrating, in relation to a human eye, not only a preferred and best-mode form of an optical system which is operable to implement and practice the methodology of the present invention, but also, as will be discussed later herein, certain modified forms of the invention, including a single-light-source modification respecting which certain system components illustrated in the figure will effectively be treated as being absent.
- FIG. 2 is an enlarged, fragmentary, cross-sectional view of the front portion of the eye shown in FIG. 1 , specifically illustrating a representative pathway of a beam of light incident on the front portion of eye, and of resulting internal and outbound reflections which occur in accordance with practice of the invention— the internal reflections taking place within the cornea, and specifically including reflections from the optical interface which exists between the rear surface of the cornea and the aqueous humor.
- FIG. 1 indicated generally in a downwardly-looking plan view at 10 in FIG. 1 is an integrated optical, computer and electronic system constructed to perform, in a preferred and best-mode manner, the eye-property monitoring methodology of the present invention.
- System 10 appears is pictured in full operative association with a human eye which is shown at 12 .
- FIG. 2 illustrates, in a greatly enlarged, fragmentary, and cross-sectional manner, the front portion of eye 12 which includes the well-known ring-shaped region 14 (edges only of which are shown) known as the limbus, a structure that essentially surrounds the outwardly convexly-shaped cornea 16 .
- the concavely-shaped inner, or back, surface of cornea 16 forms one side of an optical interface with the aqueous humor shown at 18 .
- a representative line-of-sight for eye 12 is shown by a dash-dot line 20 in both drawing figures.
- system 10 includes two light-emitting-diode (LED) light sources, or light-source structure, 22 , 24 , an appropriate (regarding light-source wavelengths), conventional optical beam combiner 26 , three lenses, shown at 28 , 30 , 32 , an elongate optical fiber 34 having input and output ends 34 a , 34 b , respectively, two photodiodes, photodetectors, or optical monitoring structure, 36 , 38 , a suitably algorithmically programmed digital computer, or result-determining structure, 40 , and a screen display 42 .
- Appropriate control and data-flow connection lines 44 , 46 , 48 , 50 , 52 connect computer 40 to light source 22 , light source 24 , photodiode 36 , photodiode 38 , and screen display 42 , respectively.
- Interposed computer 40 and each of control connection lines 44 , 46 are an appropriate, conventional, upstream, single, digital-to-analogue converter, and downstream from this converter, and intermediate the converter and the mentioned, two control connection lines, a control-connection-line-shared LED switching and operating-current-level controller.
- the performances of these two, conventional electronic devices (the converter and the controller) which lie between the computer and sources 22 , 24 will be explained shortly.
- Light source 22 is a near infrared source operating at a wavelength of about 850-plus-or-minus-about-30-nanometers
- light source 24 is a green source operating at a wavelength of about 540-plus-or-minus-about-30-nanometers.
- these two light sources are specifically operated, i.e., energized, under the control of computer 40 through control connections 44 , 46 , respectively. They are operated, one immediately after the other, preferably at a 50% duty cycle, and at a common light-output power level (i.e., at equal power levels).
- the common power level, established by computer 40 , for these sources is that which is considered to be appropriate for illuminating, without harming, the limbus of the human eye, and so as to be certain produce the pattern of useful internal and output reflections which has been referred to above, and which will shortly be described in more detail below.
- Those skilled in the art will naturally and readily choose an appropriate power level according to their wishes, and to their selected operating environment and determined task, and accordingly, no specific power level is set forth herein.
- the two light sources are operated at a common power level, they could be operated at different, respectively constantly maintained power levels so as to create not only this condition, but also the then associated condition of having a constant power-level differentiation.
- this source would simply be operated at the appropriate constant power level.
- the above-mentioned light-source wavelengths have been chosen specifically to differentiate significantly the respective interactions (levels of “optical activity, or interactivity”) which they experience with glucose, and specifically with the stated near infrared source wavelength being more optically active with glucose than the stated wavelength of the green source.
- Light sources 22 , 24 are deployed in system 10 orthogonally relative to one another, and effectively on opposite functional sides of previously mentioned, conventional beam combiner 26 which functions to “combine” the transmissions of light beams from the sources to establish a condition of incidence-light-transmission along a common incidence-illumination line, or path, shown by a dash-dot line 54 in the figures.
- the direction of illumination-light incidence is indicated by an arrow 56 — this illumination passing through lens 28 which focuses the incident illumination at a spot location, or region, 14 a adjacent the right side of limbus 14 as seen in FIG. 2 in the drawings.
- the input end 34 a in optical fibre 34 detects illumination from the two sources downstream from lens 28 , as indicated in FIG. 1 , and feeds this detected illumination in the direction indicated by an arrow 58 , along an optical path shown by a dash-dot line 60 , through previously mentioned lens 30 which focuses fibre-detected illumination onto photodiode 36 .
- Information drawn from illumination thus received by photodiode 36 via the optical fibre is supplied through the previously mentioned (but not illustrated), associated signal amplifier and analogue-to-digital converter series circuit, and therefrom through data-flow connection line 48 as an input for and to computer 40 .
- incident illumination disposed along line 54 and which strikes limbus region 14 a adjacent the right side of limbus 14 in this figure, initiates a pattern of cornea-based reflections, including a sub-pattern of multiple internal reflections, represented by a zigzag dashed line 62 , and ultimately what is referred to herein as a resulting outbound reflection exiting the cornea adjacent its left side in the figure along a dash-dot line 64 in the direction indicated by an arrow 66 .
- lines 54 , 64 each lie at an angle of 45° relative to line 20 which represents the line of sight of eye 12 . As mentioned earlier, these angles are not illustrated with exactness in the drawing figures.
- Reflection light disposed along reflection line 64 flowing in the direction of arrow 66 , passes through previously mentioned lens 32 which creates a reflection image focused on photodiode 38 .
- Information contained in this reflection illumination which is received by photodiode 38 is supplied through the previously mentioned (but not illustrated), associated signal amplifier and analogue-to-digital series circuit, and therefrom through data-flow connection line 50 to computer 40 .
- computer 40 is initially appropriately programmed to handle all relevant computer-control and data-response and monitoring functions to be associated with practice of the invention methodology.
- circuitry described above which connects the computer to light sources 22 , 24 via control connection lines 44 , 46 , respectively, and by operation of the computer, these light sources are energized in a fashion whereby, in the particular practice of the methodology of the invention which will now be described, and as has been mentioned above as one preferred manner of operation, the light-output power levels of these two light sources are essentially equalized.
- Beam combiner 26 combines the light beams generated by sources 22 , 24 —these beams being created in a 50% duty cycle, alternating fashion under the control of computer 40 — and feeds the combined light beams toward and through lens 28 along common illumination-incidence line, or path, 54 .
- the input end 34 a of optical fiber 34 effectively, collects portions of these combined beams, and feeds collected, combined-beam information to its output end 34 b which effectively sits at a focal point of lens 30 , thus to create a related light-beam flow along path, or line, 60 through lens 30 to strike, at its other focal point, photodiode 36 .
- Data-flow connection line 48 Information/data relevant to what thus impinges photodiode 36 is supplied through data-flow connection line 48 , and the previously mentioned, associated electronic circuitry, to computer 40 , which, utilizing this information as feedback information, operates appropriately to control the energizations of sources 22 , 20 or to achieve the power-output equalizations just mentioned above.
- light source 22 is a near infrared source
- source 24 is a green source
- what results from energizing of these two sources is a combinational, alternating, red/green beam which flows along off-line-of-sight-axis- 20 line 54 , directed toward a focused spot which, with the system components properly positioned relative to a person's eye, such as eye 12 , coincides with a fundus region, such as region 14 a in fundus 14 of eye 12 .
- the focused, combinational beam when it strikes a fundus region like region 14 a , produces a pattern of reflections, such as the pattern shown in FIG. 2 , including plural, eye-internal reflections like those represented by zigzag line 62 , and a final, resulting outbound reflection, such as that shown by line 64 .
- the outbound reflection will be characterized by reflection-intensity-level differences in the two components (infrared and green) of the out bound reflection beam flowing toward lens 32 along line 64 .
- Lens 32 focuses the outbound-reflection, combinational beam onto photodiode 38 , data from which is then supplied by data-flow connection line 50 , and the previously described electronic circuitry which is associated with that line, as another input for and to computer 40 .
- computer 40 utilizing its appropriate algorithmic programming (mentioned earlier) will, in relation to the practice illustration now being presented, generate an output indication of blood-glucose concentration.
- This blood-glucose output information may be furnished to a user in a number of different well-known ways, including by presenting information on screen display 42 .
- system 10 be disposed relative to a person's eye to have a correct deployment disposition, such as that represented schematically in FIG. 1 .
- relative positioning established between the components of system 10 and a person's eye may be accomplished under computer control whereby computer 40 drives appropriate motors which multi-axially adjusts the positions of system components, which components may be supported, in any appropriate conventional manner, on a common framework.
- System adjustments during calibration will, of course, take place under circumstances where an eye to be examined/monitored is ultimately properly in place, in the sense that a person is ultimately appropriately seated and stabilized.
- a person regarding whom calibration is to be performed is placed in a near-correct position relative to the system elements.
- System adjustment then takes place, for example, by the presentation on screen display 42 of a spot of light respecting which the “examined” person is asked to focus his or her to-be-looked-at eye focused on that light spot.
- System positional adjustments are then made effectively to maximize outbound eye-reflection readings detected by photodiode 38 .
- This curve is then entered into computer 40 , and once entered, furnishes an appropriate, person-specific calibration for determining noninvasive blood glucose concentration for that person based upon system 10 readings.
- person-specific calibration needs to be repeated at regular intervals, such as, for example, every six months. (Such a re-calibration frequency will typically be determined during clinical trials).
- one modified form of the invention methodology is one wherein a system constructed to implement it employs only a single light source, such as light source 22 . Accordingly, looking now at FIG. 1 with this modification in mind, one should ignore the presences of light source 24 and of beam combiner 26 which would not be employed in such a modification.
- Light source 22 would, of course, be employed, and in the context of monitoring, glucose concentration, would be, as it is currently described, a near infrared source.
- the light beam which is directed from source 22 , along line 54 , through lens 28 to limbus region 14 a is a single-wavelength beam, the source 22 for which could be operated by computer 40 either continuously or intermittently, as desired.
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US13/366,299 US8639306B2 (en) | 2011-02-07 | 2012-02-04 | Noninvasive eye-property monitoring, including aqueous-humor glucose monitoring as an indication of blood glucose level |
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US201161462677P | 2011-02-07 | 2011-02-07 | |
US13/366,299 US8639306B2 (en) | 2011-02-07 | 2012-02-04 | Noninvasive eye-property monitoring, including aqueous-humor glucose monitoring as an indication of blood glucose level |
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US20160249881A1 (en) * | 2015-02-26 | 2016-09-01 | Sperion Medical Devices Llc | Perioperative Ocular Distention (POD) Monitor |
US9442065B2 (en) | 2014-09-29 | 2016-09-13 | Zyomed Corp. | Systems and methods for synthesis of zyotons for use in collision computing for noninvasive blood glucose and other measurements |
US9554738B1 (en) | 2016-03-30 | 2017-01-31 | Zyomed Corp. | Spectroscopic tomography systems and methods for noninvasive detection and measurement of analytes using collision computing |
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US9597020B2 (en) * | 2012-10-16 | 2017-03-21 | Electronics And Telecommunications Research Institute | Measuring device and glucose concentration measurement method of the measuring device |
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US9459203B2 (en) | 2014-09-29 | 2016-10-04 | Zyomed, Corp. | Systems and methods for generating and using projector curve sets for universal calibration for noninvasive blood glucose and other measurements |
US9459202B2 (en) | 2014-09-29 | 2016-10-04 | Zyomed Corp. | Systems and methods for collision computing for detection and noninvasive measurement of blood glucose and other substances and events |
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WO2012109116A3 (en) | 2013-04-25 |
US20120215079A1 (en) | 2012-08-23 |
WO2012109116A2 (en) | 2012-08-16 |
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